Founder effect in a Belgian-Dutch fragile X population

For many years, the high prevalence of the fragile X syndrome was thought to be caused by a high mutation frequency. The recent isolation of the FMR1 gene and identification of the most prevalent mutation enable a more precise study of the fragile X mutation. As the vast majority of fragile X patients show amplification of an unstable trinucleotide repeat, DNA studies can now trace back the origin of the fragile X mutation. To date, de novo mutations leading to amplification of the CGG repeat have not yet been detected. Recently, linkage disequilibrium was found in the Australian and US populations between the fragile X mutation and adjacent polymorphic markers, suggesting a founder effect of the fragile X mutation. We present here a molecular study of Belgian and Dutch fragile X families. No de novo mutations could be found in 54 of these families. Moreover, we found significant (P < 0.0001) linkage disequilibrium in 68 unrelated fragile X patients between the fragile X mutation and an adjacent polymorphic microsatellite at DXS548. This suggests that a founder effect of the fragile X mutation also exists in the Belgian and Dutch populations. Both the absence of new mutations and the presence of linkage disequilibrium suggest that a few ancestral mutations are responsible for most of the patients with fragile X syndrome.     

Founder effect and genetic disease in Sottunga, Finland

Pedigree data are analyzed in order to determine the factors responsible for the high frequencies of certain genetic disorders in an isolated Swedish-speaking population of Finland's A land archipelago. The founders of Sottunga are identified, and the genetic contributions of each founder to descending birth cohorts are estimated. Founders born before 1700 have far more descendants in the contemporary gene pool than do more recent founders. However, because of migration and depopulation since 1900, the expected genetic contributions of the early founders to the present-day population are similar to those of later founders. A descendant in the contemporary population has a 2% chance of having inherited a particular gene from the founder who makes the largest single contribution to the gene pool. This corresponds approximately to a 2% probability of inheriting an autosomal dominant disease gene from this founder. Given an average inbreeding coefficient of 0.0016, the probability of inheriting two recessive disease genes from this founder is 0.000032. The incidence of autosomal dominant von Willebrand disease in Sottunga is greater than 10% while that of autosomal recessive tapetoretinal disease is 1.5%. We conclude, therefore, that the high frequencies of these diseases are not due to the disproportionate genetic contribution of one or a few particular founders. It is more likely that these disease genes occurred in high frequency in the initial population or were introduced repeatedly through time.     

Founder effect in familial hyperchylomicronemia among French Canadians of Quebec

Familial hyperchylomicronemia has reached a high prevalence in the French Canadian population of eastern Quebec. The birth places of 58 carriers identified through the birth of one affected child clustered in three regions. The genealogies of these 58 individuals showed that no founder was common to all of them. Three sets of founders were found, one for each region, with little overlapping between two regions. These results strongly suggest that more than one mutation, introduced by the French migrants in the 17th century, are segregating in the French Canadian population. Perche, a region situated between Paris and Normandy, appeared to be the most likely putative center of diffusion of at least one mutation in the lipoprotein lipase gene segregating in the modern-day French Canadian population of Quebec.     

Founder effect in a young Leccinum duriusculum (Schultzer) Singer population

The genetic diversity of a Leccinum duriusculum population growing under <20-year-old Populus alba on former farming soil was analysed from 1998 to 2001 and compared in 2000 to the two nearest populations found under >70-year-old P. alba. Genets were recognized using RAPD amplifications with three different primers, while their conspecificity was assessed by sequencing the nuclear ITS and mitochondrial large ribosomal subunit. The young population was colonized by a large genet that persisted from 1998 to 2001 (most distal sporophores were 10.4 m apart in 2001) and a second genetically related genet appeared in 2001. Five and six genets, respectively, of smaller size were found in the two other populations, while the investigated area was slightly smaller (72.25 m2) and the three populations were strongly divergent genetically (>33%). The genetic uniformity, as well as the high speed of radial growth of the lasting genet under <20-year-old P. alba (radial growth: 1 m/year), are interpreted in the framework of a founder effect. The slow recruitment of genets is proposed to lower the intraspecific competition and to entail large, fast-growing genets. The differences from ectomycorrhizal populations due to secondary colonization, which have been investigated often, are also emphasized.     

Founder effect and bottleneck signatures in an introduced,insular population of elk

The population of elk (Cervus elaphus roosevelti) inhabiting Afognak Island, Alaska, USA arose from an introduction of 8 individuals from an established population in Washington, USA in 1929, and recently peaked at approximately 1,400 individuals. We examined indices of diversity for 15 microsatellite loci in the Afognak population and compared them to levels in the parent population to determine effects of translocation and demography on genetic variation. The Afognak population differed significantly (P < 0.0001) from the source population in both allele and genotype frequencies. Allelic richness, number of private alleles and multilocus heterozygosity, but not percent loci polymorphic, were significantly lower in Afognak elk. Mean inbreeding coefficients within Afognak (f = 0.019) and source (f = −0.006) populations did not differ significantly from zero. Despite the demographic bottleneck, no evidence of a genetic bottleneck in the Afognak population was detected using a test for heterozygosity excess or mode shift of allele frequencies. Simulations indicated that rapid population growth after the translocation resulted in heterozygosity excess for only 8 years. Conversely, a statistic testing for a bottleneck signature in the ratio of allele number to allele size range (M-ratio) was significant for both the Afognak and source populations, suggesting that the Afognak population had effectively undergone serial bottlenecks. Nonetheless, Afognak failed to show a smaller M-ratio than the parent population, suggesting a failure of that statistic to detect the bottleneck associated with introduction. We show that a severe bottleneck followed by rapid population growth may be undetectable using available tests.     

Founder cell specification

Lateral organs arise from individual or groups of cells either on the flanks of meristems or within defined cellular positional contexts. The first event in organogenesis is founder cell specification. Auxin is one necessary signal in different organ specification contexts, but it is difficult to distinguish between correlative and causal signals and evidence is emerging that other signals exist and that the interplay between these signals is important for organ initiation. This review analyses the progress in understanding which signals contribute to founder cell specification and outlines the emerging complexities in the perception of positional information that are context-dependent and reliant on the establishment and coordination of different types of competencies.     

Founder mutations in the Netherlands

In this part of a series on founder mutations in the Netherlands, we review a Dutch family carrying the SCN5a 1795insD mutation. We describe the advances in our understanding of the premature sudden cardiac deaths that have accompanied this family in the past centuries. The mutation carriers show a unique overlap of long-QT syndrome (type 3), Brugada syndrome and progressive cardiac conduction defects attributed to a single mutation in the cardiac sodium channel gene SCN5a. It is at present one of the largest and best-described families worldwide and we have learned immensely from the mouse strains with the murine homologue of the SCN5a 1795insD mutation (SCN5a 1798insD). From the studies currently performed we are about to obtain new insights into the phenotypic variability in this monogenic arrhythmia syndrome, and this might also be relevant for other arrhythmia syndromes and the general population. (Neth Heart J 2009;17:422–8.)     

Founder effect and prevalence of myotonic dystrophy in South Africans: molecular studies.

A high prevalence of myotonic dystrophy (DM) has been described in South African Caucasoid Afrikaans-speaking families in the northern Transvaal. Evidence is presented for a strong founder effect, with a single haplotype occurring on 68% of all Caucasoid DM chromosomes; among the Afrikaans speakers, the proportion was 83%. In addition to this major haplotype, five minor DM haplotypes in the Caucasoids and two minor haplotypes in DM individuals of mixed ancestry were found. All DM chromosomes, however, had a common haplotype core, namely, Alu (ins), HinfI-2 (intron 9), and TaqI-2 (D19S463). We have detected significant linkage disequilibrium between the DM mutation and particular alleles of the extragenic markers D19S112 and D19S207. Significant differences were found in allele and haplotype distributions in the Caucasoid DM and non-DM chromosomes and Negroid non-DM chromosomes. These findings together with the strong association of allele 3 at the D19S63 locus on 93% (14/15) of the South African DM chromosomes suggest that the majority of present-day DM mutations in South African Caucasoids may have originated from a common initial founder who introduced one of the European ancestral mutations.     

Founder effects,post-introduction evolution and phenotypic plasticity contribute to invasion success of a genetically impoverished invader

Oecologia - Multiple mechanisms may act synergistically to promote success of invasive plants. Here, we tested the roles of three non-mutually exclusive mechanisms—founder effects,...     

Founder mitochondrial haplotypes in Amerindian populations.

It had been proposed that the colonization of the New World took place by three successive migrations from northeastern Asia. The first one gave rise to Amerindians (Paleo-Indians), the second and third ones to Nadene and Aleut-Eskimo, respectively. Variation in mtDNA has been used to infer the demographic structure of the Amerindian ancestors. The study of RFLP all along the mtDNA and the analysis of nucleotide substitutions in the D-loop region of the mitochondrial genome apparently indicate that most or all full-blooded Amerindians cluster in one of four different mitochondrial haplotypes that are considered to represent the founder maternal lineages of Paleo-Indians. We have studied the mtDNA diversity in 109 Amerindians belonging to 3 different tribes, and we have reanalyzed the published data on 482 individuals from 18 other tribes. Our study confirms the existence of four major Amerindian haplotypes. However, we also found evidence supporting the existence of several other potential founder haplotypes or haplotype subsets in addition to the four ancestral lineages reported. Confirmation of a relatively high number of founder haplotypes would indicate that early migration into America was not accompanied by a severe genetic bottleneck.     

Founder effects and genetic variability in Quebec

Knowledge of the genetic population structure lies at the heart of mapping studies aiming genes responsible for Mendelian and complex traits. The Quebec population, which is of mostly French descent, is considered an excellent model for such genetic epidemiological endeavours because it is a young founder population. Yet, the assessment of the founder effect has relied mostly on the observed distribution of monogenic diseases and on the analysis of the underlying mutations with investigations focusing on the Saguenay region. To eliminate this clinical bias and to obtain a more complete image of the genetic diversity, different regional populations of Quebec were investigated by analysing neutral markers that represent maternal, paternal and X chromosome lineages. Results indicate that Quebec does not appear more homogeneous nor significantly different from European populations. However, a series of regional founder effects, particularly visible at the level of rare variants, are observed. These effects can be explained by the successive migrations of descendants of the first immigrants from the initial sites of settlement towards the outer regions. Depending on the number of founders and their diversity, as well as on the degree of isolation and the magnitude of the interbreeding with the neighbouring or local populations, such as Amerindians or later migrants, the consequences of these regional founder effects are more or less detectable in the contemporary population.     

Native American Admixture in the Quebec Founder Population

For years, studies of founder populations and genetic isolates represented the mainstream of genetic mapping in the effort to target genetic defects causing Mendelian disorders. The genetic homogeneity of such populations as well as relatively homogeneous environmental exposures were also seen as primary advantages in studies of genetic susceptibility loci that underlie complex diseases. European colonization of the St-Lawrence Valley by a small number of settlers, mainly from France, resulted in a founder effect reflected by the appearance of a number of population-specific disease-causing mutations in Quebec. The purported genetic homogeneity of this population was recently challenged by genealogical and genetic analyses. We studied one of the contributing factors to genetic heterogeneity, early Native American admixture that was never investigated in this population before. Consistent admixture estimates, in the order of one per cent, were obtained from genome-wide autosomal data using the ADMIXTURE and HAPMIX software, as well as with the fastIBD software evaluating the degree of the identity-by-descent between Quebec individuals and Native American populations. These genomic results correlated well with the genealogical estimates. Correlations are imperfect most likely because of incomplete records of Native founders’ origin in genealogical data. Although the overall degree of admixture is modest, it contributed to the enrichment of the population diversity and to its demographic stratification. Because admixture greatly varies among regions of Quebec and among individuals, it could have significantly affected the homogeneity of the population, which is of importance in mapping studies, especially when rare genetic susceptibility variants are in play.     

Founder mutations in hypertrophic cardiomyopathy patients in the Netherlands

In this part of a series on cardiogenetic founder mutations in the Netherlands, we review the Dutch founder mutations in hypertrophic cardiomyopathy (HCM) patients. HCM is a common autosomal dominant genetic disease affecting at least one in 500 persons in the general population. Worldwide, most mutations in HCM patients are identified in genes encoding sarcomeric proteins, mainly in the myosin-binding protein C gene (MYBPC3, OMIM #600958) and the beta myosin heavy chain gene (MYH7, OMIM #160760). In the Netherlands, the great majority of mutations occur in the MYBPC3, involving mainly three Dutch founder mutations in the MYBPC3 gene, the c.2373_2374insG, the c.2864_2865delCT and the c.2827C>T mutation. In this review, we describe the genetics of HCM, the genotype-phenotype relation of Dutch founder MYBPC3 gene mutations, the prevalence and the geographic distribution of the Dutch founder mutations, and the consequences for genetic counselling and testing. (Neth Heart J 2010;18:248-54.)     

The positive effect of role models in evolution instruction

Background

Previous research has identified numerous factors to explain why students have difficulty learning about evolution. Some of these factors include a student’s background (including their religion and major of study), the type of evolution instruction, and the inclusion of the nature of science (NOS) instruction. Sparse but more recent work has investigated the impact of a religious-scientist role model to help dampen perceptions of conflict between evolutionary science and worldview. We had two research goals: (1) to identify which of these factors influence students’ learning of evolution in post-secondary education; and (2) to describe the relationships among incoming biology students’ creationist reasoning, knowledge of evolution, and perceived conflict between evolution and their worldview.

Results

The single factor linked with the reduction in both creationist reasoning and in students’ perceived conflict between evolution and their worldview through a semester was the presence of a role model. Likewise, knowledge and perceived relevance of evolution increased in sections with a role model instructor and with evidence-based evolution instruction. Otherwise, tested factors (the type of evolution instruction, inclusion of NOS, biology-major/nonmajor, GPA, or religiosity) were not shown to be associated with these three constructs. We found that in the first week of the semester students with higher knowledge of evolution had lower creationist reasoning and lower perceived conflict.

Conclusions

The single factor that collectively reduced erroneous beliefs, increased scientific knowledge, and minimized perceived conflict was the presence of a religious-scientist role model. Previous work has suggested a role model could positively impact students’ learning of evolution, yet this is the first quasi-experimental evidence supporting the importance of the course instructor as the role model in students’ learning of evolution. These findings are especially relevant to institutions with a greater proportion of religious students who could benefit from modeling to help foster their learning of evolution.

     

The effect of evolution on host-parasitoid systems

It is well known that a simple first-order difference equation can exhibit complex population dynamics, such as sustained oscillations and chaos. An interesting problem is whether such oscillatory dynamics are expected to occur in real populations. This paper assumes that the resident system is composed of 1-host and 1-parasitoid and that only the host is allowed to evolve, but not the parasitoid. Based on the invasibility of a host to host-parasitoid systems, we investigate the dynamics of the host-parasitoid system favored by natural selection. We consider two cases. In the first case, the host's evolution involving both the intrinsic growth rate and the sensitivity to density is considered. In the second case, the host's evolution involving both the intrinsic growth rate and the vulnerability to the parasitoid is considered. In both cases, we see that the dynamics with a stable equilibrium will not be favored by natural selection without the trade-off between the host's traits which are allowed to evolve. The host-parasitoid system with a stable equilibrium will be eventually invaded by a host type that develops an unstable equilibrium with the parasitoid. If there is a trade-off between the host's traits which are allowed to evolve, a host-parasitoid system with a stable equilibrium can be favored by natural selection.